Human Rhinovirus/Enterovirus in Pediatric Acute Respiratory Distress Syndrome.
The role of human rhinovirus/enterovirus (HRV/HEV) in severe lower respiratory tract infections remains unclear. We characterized the respiratory status of children admitted to a large academic pediatric intensive care unit (PICU) who tested positive for only HRV/HEV. One hundred and fifty-five children met inclusion criteria with 62% requiring positive pressure respiratory support of 5 cm of water pressure or more within the first 24 hours of admission. Among them, 34% had SaO 2 to FiO 2 ratios of 264 or less with 22 patients (14%) meeting criteria for pediatric acute respiratory distress syndrome. HRV/HEV is associated with significant respiratory disease in children admitted to the PICU.


Evaluation of quantitative ultrasound tissue characterization of the cervix and cervical length in the prediction of premature delivery for patients with spontaneous preterm labor.
This study was to evaluate the predictive value of the uterine cervix tissue with the use of quantitative ultrasound gray level analysis for preterm delivery. Sixty-eight patients with preterm labor between 20 and 35 weeks of gestation were included. When two-dimensional transvaginal ultrasound measurement of cervical length was completed, a region of interest of constant size was defined in the midsection of the posterior wall, and the tissue-specific gray scale was determined. Preterm delivery of <37 weeks of gestation was sought. Twenty-eight patients (41.2%) were delivered preterm. The risk for preterm delivery was increased significantly in patients with cervical length of </=2.5 cm (odds ratio, 7.67; 95% CI, 2.4-24.45), with Bishop score of >/=4 (odds ratio, 3.44; 95% CI, 1.21-9.75), and with decreased mean gray scale value (odds ratio, 12.13; 95% CI, 3.69-39.88). Parity and uterine contractions were not significant as predictors for preterm delivery, although the risk for preterm delivery increased with higher parity (odds ratio, 1.8; 95% CI, 0.68-4.79). The risk for preterm delivery remained nearly the same by uterine contractions (odds ratio, 0.92; 95% CI, 0.28-3.01). A mean scale value of </=6.54 had the best cutoff value for the prediction of preterm delivery. For preterm delivery, a mean gray value </=6.54 had a sensitivity of 82.1%, a specificity of 72.5%, a positive predictive value of 67.6%, and a negative predictive value 85.3%. Multiple logistic regression analysis indicated that, even when other variables are considered simultaneously, the mean gray scale value is the single best predictor of preterm delivery. Quantitative ultrasound tissue characterization of the uterine cervix predicts premature delivery and provides additional information in the prediction of potential premature delivery.


Complete Genome Sequence of a Bovine Ephemeral Fever Virus Isolate from Israel.
Here, we report the first complete genome of a bovine ephemeral fever virus (BEFV) isolate from an infected bovine in Israel. The genome shares 95.3% identity with a Turkish genomic sequence but contains α3 and γ open reading frames that are truncated compared to those of existing BEFV genome sequences.


Heuristics in Managing Complex Clinical Decision Tasks in Experts' Decision Making.
Clinical decision support is a tool to help experts make optimal and efficient decisions. However, little is known about the high level of abstractions in the thinking process for the experts. The objective of the study is to understand how clinicians manage complexity while dealing with complex clinical decision tasks. After approval from the Institutional Review Board (IRB), three clinical experts were interviewed the transcripts from these interviews were analyzed. We found five broad categories of strategies by experts for managing complex clinical decision tasks: decision conflict, mental projection, decision trade-offs, managing uncertainty and generating rule of thumb. Complexity is created by decision conflicts, mental projection, limited options and treatment uncertainty. Experts cope with complexity in a variety of ways, including using efficient and fast decision strategies to simplify complex decision tasks, mentally simulating outcomes and focusing on only the most relevant information. Understanding complex decision making processes can help design allocation based on the complexity of task for clinical decision support design.


Survey of transplant-related pharmacy services at large comprehensive transplant centers in the United States.
United Network for Organ Sharing (UNOS) 2011 bylaws and Centers for Medicare and Medicaid Services (CMS) regulations require a transplant pharmacist to be an active participant in the care of transplant patients. Transplant centers must be members in good standing with UNOS in order to perform transplants and must be certified by CMS to participate with Medicare. To identify characteristics of transplant-related pharmacy services at comprehensive transplant centers. Survey regarding number of full-time equivalent (FTE) transplant pharmacists relative to number of annual transplants, transplant pharmacy model, roles in inpatient and clinic environments, training and specialization, funding sources, and expansion plans.Participants-Surveys were received from 14 (74%) of 19 identified centers that performed 200 to 400 kidney, liver, pancreas, simultaneous kidney/pancreas, heart, and lung transplants in 2010, representing 55 transplant pharmacists. A mean of 325 transplants were performed in 2010 at the surveyed centers. The mean number of pharmacist FTEs was 4.25, which yielded a transplant-to-pharmacist ratio of 76.5. Nine centers (64%) practiced in a pharmacy specialist-only model, 12 (86%) practiced in a service-based fashion, and 10 (71%) saw patients in clinic. Fifty-four pharmacists (98%) had obtained a PharmD degree, 45 (82%) had completed 1 postgraduate year, and 28 (51%) had completed 2 postgraduate years of training. Nine centers (64%) funded FTEs solely through the pharmacy department. Ten centers (71%) plan to expand transplant pharmacist staff by a mean of 1.4 FTEs. Large comprehensive transplant centers use multiple transplant pharmacists to perform patient care in the inpatient and outpatient environments. Most centers plan to expand FTEs. Further characterization of transplant pharmacists appears warranted.


[Role of corticoid-antibiotic combinations in local treatments. Critical study].
Current literature about steroid antibiotic combinations has been critically reviewed. The use of such combinations may be considered in infected steroid sensitive dermatosis. Definition of super-infection is however impossible on clinical data only. A single study demonstrated the superiority of the combination upon the steroid alone in well defined experimental conditions. This superiority is not demonstrated beyond 8 days of treatment or in case of pretreatment with local antiseptic solutions or baths. Theoretical side effects of local antibiotics include, sensitization, selection of antibiotic resistant germs, systemic toxicity. They are not troublesome in current practice. However adjunctions of an antibiotic can diminish the steroid efficacy when infection is not present. The real usefulness of the combination in current practice is still to be demonstrated.


The synthesis and evaluation of quinolinequinones as anti-mycobacterial agents.
A library of thirty-two quinolinequinones (QQs) with various amine substituents at the 6- and 7-positions were synthesised efficiently and in good yields for evaluation as potential anti-tuberculosis agents. Mycobacterium tuberculosis growth inhibition assays demonstrated that QQs bearing moderate length alkyl chains (i.e. heptylphenylamino- and octylamino-QQs), and aryl groups (i.e. phenylethylamino- and benzylamino-QQs) exhibited encouraging inhibitory activity, while QQ analogue 7-chloro-6-propargylamino-quinoline-5,8-dione (16b) had excellent inhibitory activity (MIC = 8 μM). The cLogP values and redox activities of the QQs were determined, and neither readout correlated with the anti-mycobacterial activities of the compounds. Notwithstanding, mode of action studies of 16b revealed that treatment of M. tuberculosis with this compound led to activation of NADH-dependent oxygen consumption suggesting a redox cycling mechanism. To this end, the promising anti-mycobacterial activity of several QQs and their ability to perturb oxygen management leading to an uncontrolled respiratory burst, as identified in this work and by others, demonstrates the merit of further optimising the anti-mycobacterial activity of this readily synthesised class of compound.


Anatomic investigations of nerves at the wrist: I. Orientation of the motor fascicle of the median nerve in the carpal tunnel.
The orientation of the motor fascicle of the median nerve in the carpal tunnel was investigated in dissections of 50 hands. Topographically, the motor branch was located on the radial-volar aspect of the median nerve in 60% of the hands, the central-volar aspect in 22%, and between these two locations in the remaining 18%. In 56% of the hands, the motor branch passed through a separate distinct fascial tunnel before entering the thenar muscles. Awareness of these patterns will facilitate appropriate surgical management of thenar muscle weakness or wasting associated with the carpal tunnel syndrome.


Two to three years of failure-free testing of a rechargeable pacemaker in experimental complete heart block.
Six hermetically sealed single cell rechargeable mercury-zinc pacemakers (B.T.) that will run continuously for over 4 years between rechargings have paced dogs with complete heart block for from 2 to 3 years. To maintain full cell capacity (over 1,000 mA hours) requires recharging for from 2-3 min/day to 60 to 80 hr once every 4 years, with any variation between these extremes being acceptable. Six realtime bench tests continue after over 7 years and accelerated tests have simulated a minimum of 50 years continuous pacing. Battery voltage is assessed by direct telemetry, eliminating the risk of patient intrinsic rhythm-pacemaker competition which is present with all current indirect (stimulation rate change) battery assessment techniques. The B.T. is an excellent 4-5 year primary pacemaker, fully rechargeable after several 4 year periods of battery rundown. A clinical test series has been initiated.


Perception of the Food and Drug Administration Electronic Cigarette Flavor Enforcement Policy on Twitter: Observational Study.
On January 2, 2020, the US Food and Drug Administration (FDA) released the electronic cigarette (e-cigarette) flavor enforcement policy to prohibit the sale of all flavored cartridge-based e-cigarettes, except for menthol and tobacco flavors. This research aimed to examine the public perception of this FDA flavor enforcement policy and its impact on the public perception of e-cigarettes on Twitter. A total of 2,341,660 e-cigarette-related tweets and 190,490 FDA flavor enforcement policy-related tweets in the United States were collected from Twitter before (between June 13 and August 22, 2019) and after (between January 2 and March 30, 2020) the announcement of the FDA flavor enforcement policy. Sentiment analysis was conducted to detect the changes in the public perceptions of the policy and e-cigarettes on Twitter. Topic modeling was used for finding frequently discussed topics about e-cigarettes. The proportion of negative sentiment tweets about e-cigarettes significantly increased after the announcement of the FDA flavor enforcement policy compared with before the announcement of the policy. In contrast, the overall sentiment toward the FDA flavor enforcement policy became less negative. The FDA flavor enforcement policy was the most popular topic associated with e-cigarettes after the announcement of the FDA flavor enforcement policy. Twitter users who discussed about e-cigarettes started to talk about other alternative ways of getting e-cigarettes after the FDA flavor enforcement policy. Twitter users' perceptions of e-cigarettes became more negative after the announcement of the FDA flavor enforcement policy.


[Molecular Identification and Phylogenetic Analyses of Coxsackievirus A24v Causing an Outbreak of Acute Hemorrhagic Conjunctivitis in Jiangxi, China, in 2010].
To identify the cause of an outbreak of acute hemorrhagic conjunctivitis (AHC) in Jiangxi (China) in 2010, 20 eye conjunctival swabs were first collected from AHC patients. Then, viruses were isola- ted and tested for human enterovirus 70, coxsackievirus A24 variant (CV-A24v) and adenovirus using the polymerase chain reaction. All CV-A24v isolates underwent sequencing of 3C and VP1 coding regions. Then, a phylogenetic tree was constructed for Jiangxi CV-A24v and worldwide CV-A24v based on,3C and VP1 regions, respectively. Ten out of 20 specimens were positive for CV-A24v, implying that the outbreak was caused by CV-A24v. The phylogenetic tree based on the 3C region showed that Jiangxi CV- A24v belonged to cluster 5 in genotype IV (GIV-C5) with strains isolated throughout the world after 2010, and were divided further into A and B lineages. Phylogenetic analyses of the VP1 region showed that all of the worldwide CV-A24v strains isolated after 2000 could be divided into five groups (1-5). Jiangxi CV-A24v was classified into group 5 and also divided further into A and B lineages upon analyses of the 3C region. These data suggested that CV-A24v causing AHC outbreaks in China in 2010 belonged to GIV-C3 and GIV-C5. At least two transmission lineages were circulated in Jiangxi in 2010. The classification of CV-A24v isolated after 2010 worldwide using the phylogenetic tree based on the VP1 region was almost consistent with that based on the 3C region and also had significant chronological clustering.


Spontaneously transformed NRK cells lose their mitogenic response to epidermal growth factor.
To understand the relationship between growth factor-induced mitogenesis and spontaneous cell transformation, a clonal isolate of epidermal growth factor (EGF)-responsive NRK cells was passed in vitro until morphologically transformed variants arose. Subclones of EGF responsive (Cl-3) and EGF nonresponsive (Cl-10) NRK cells were isolated. Cl-3 cells grew as flat, contact-inhibited monolayers, while Cl-10 cells grew as rounded or spindle-shaped cells that formed dense foci. Cl-10 cells formed colonies in soft agar more efficiently (p less than 0.01) and formed larger tumors in nude mice (p less than 0.05) than Cl-3 cells. Cl-3 cells exhibited a sixfold increase in DNA synthesis in response to 1.0 nM EGF. Cl-10 cells did not increase DNA synthesis on exposure to 100 nM EGF. These different responses to EGF occurred despite similar numbers of receptors and similar receptor.binding affinities for EGF (Cl-3: 7000 receptors, Kd = 0.67 nM; Cl-10: 8000 receptors, Kd = 0.72 nM). No evidence of transforming growth factor-alpha was detected in either of these cell lines using Northern blots, Western blots, or biologic assays. We conclude that NRK cells which undergo spontaneous morphologic transformation and exhibit enhanced anchorage-independent growth lose their mitogenic response to EGF.


[Analysis of chromosome composition in interspecific embryonic stem hybrid cells of mice].
Chromosome complements of twenty hybrid clones obtained by fusion of Mus musculus embryonic stem cells (ESC) and M. caroli splenocytes were studied. Using of double-color in situ hybridization with chromosome- and species-specific probes we were able to detect the parental origin for each chromosome in hybrid cells. Based on parental chromosome ratio, all 20 hybrid clones were separated in some different groups: from the group containing practically tetraploid M. musculus genome with single M. caroli chromosomes to hybrids with dominance of M. caroli chromosome homologues. In 8 hybrid cells clones we observed prevalence of chromosomes originated from ESC in ratio from 5:1 to 3:1. Another hybrid cells clones have either equal (1:1, 1:2) ratio of M. musculus to M. caroli chromosomes or with the prevalence of ESC- (2:1) or splenocyte- (1:2) originated parental chromosome homologues. In 3 hybrid cells clones, we observed preferable segregation of ESC-originated pluripotent chromosomes. This phenomenon was found for the first time and it possibly indicates compensation of the epigenetic differences between parental chromosomes of ESC- and splenocyte-origination.


How will better products improve the sensory-liking and willingness to buy insect-based foods?
Insects have been established to be a more sustainable alternative source of protein in comparison to conventional meats, but have little appeal to those who are unfamiliar with their taste. Yet little attention has been given to understanding how more appealing products could be developed, and whether that is sufficient to encourage consumption of a culturally unusual food. By evaluating appropriate (i.e. meatball) and inappropriate (i.e. dairy drink) mealworm products along with the original mealworm-free products, this study provided new insights into how the product influences sensory-liking and willingness to buy insect-based foods for trial and regular consumption. Willing (n=135) and unwilling tasters (n=79) were recruited to explore differences between individuals who differ in their intentions to eat insects. An appropriate product context improved the expected sensory-liking and willingness to buy mealworm products once and regularly. However, consumers should first be motivated to eat insects for a better product to improve consumption intentions. Descriptive sensory profiling revealed that mealworm products were expected and experienced to taste very different from the original mealworm-free products, but were generally preferred to taste similar to the original, albeit with some unique attributes. Using a familiar and liked product preparation could help to increase trial intentions, but the product should also be appropriate and taste good if it is to be regularly consumed. We conclude that even with high interest and good products, willing consumers still hesitate to consume insect-based foods regularly due to other practical and socio-cultural factors. We recommend that future research should not only give emphasis to increasing initial motivations to try, but should address the barriers to buying and preparing insects for regular consumption, where issues relating to availability, pricing, knowledge and the social environment inhibit the uptake of this culturally new food.


Synthesis of Platinum Nanoparticles Supported on Fused Nanosized Carbon Spheres Derived from Sustainable Source for Application in a Hydrogen Generation Reaction.
The dwindling supply of fossil fuels has prompted the search for an alternative energy source that could effectively replace them. Potential renewable energy sources such as solar, wind, tidal, and geothermal are all promising but each has its own drawbacks. Hydrogen gas on the other hand can be combusted to produce energy with only water as a byproduct and can be steadily generated via the aqueous media hydrolysis reaction of Sodium Borohydride (NaBH4). This study successfully synthesized fused carbon spheres derived from sugar and decorated them with platinum nanoparticles to form a novel composite material (PtFCS) for catalyzing this reaction. The platinum nanoparticles were produced by reducing chloroplatinic acid in a solution with sodium borohydride and using sodium citrate as a capping agent for the nanoparticles. Transmission electron microscopy (TEM), Energy-dispersive X-ray spectroscopy (EDS), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD) were used to characterize and determine the size and shape of the Pt nanoparticles (PtNPs) and fused carbon spheres. TEM was able to determine the average size of the fused carbon spheres to be 200 nm and the average size for the PtNPs to be 2-3 nm. The PtFCS composite was tested for its ability to catalyze the hydrolysis of NaBH4 under various reaction conditions including various solution pH, various temperatures, and various dosages of sodium borohydride. The catalyst was found to perform the best under acidic solution conditions (pH 6), producing hydrogen at a rate of 0.0438 mL/mgcat·min. The catalyst was determined to have an activation energy of 53.0 kJ/mol and could be used multiple times in succession with no loss in the volume of hydrogen produced. This sugar-derived composite catalyst shows promise and could be implemented as a sustainable catalyst for the generation of hydrogen fuel.


Prostatic acid phosphatase as a target molecule in specific immunotherapy for patients with nonprostate adenocarcinoma.
Prostatic acid phosphatase (PAP) is one of the prostate-related antigens that are applicable to specific immunotherapy for patients with prostate cancer. In this study, we determined whether or not PAP could be a target molecule in specific immunotherapy for patients with nonprostate cancer. A variety of adenocarcinoma cell lines were examined for their PAP expression at the mRNA and protein levels by reverse transcription polymerase chain reaction and western blot analysis, respectively. Considerable percentages of colon, gastric, and breast cancer cell lines were found to be positive for PAP at both the mRNA and the protein levels. The PAP expression in cancer tissues was also confirmed by immunohistochemical staining. In addition, we examined whether cancer-reactive cytotoxic T lymphocytes (CTLs) could be induced from peripheral blood mononuclear cells (PBMCs) of human leukocyte antigen (HLA) A24+ nonprostate cancer patients by in vitro stimulation with a PAP peptide. As a result, tumor-specific CTLs could be induced from the PBMCs of HLA-A24+ colon and gastric cancer patients. Their cytotoxicity against HLA-A24+ cancer cells was dependent on PAP peptide-specific and CD8+ T cells. These findings indicate that PAP could be a target molecule in specific immunotherapy for patients with nonprostate adenocarcinomas including colon and gastric cancers.


Effect of Conidiobolus coronatus on the Cuticular and Internal Lipid Composition of Tettigonia viridissima Males.
Conidiobolus coronatus is an entomopathogenic fungus which has a potential as a biological control agent of insects. The cuticular and internal lipid composition of infected and noninfected Tettigonia viridissima males were analyzed by GC/MS. A total of 49 compounds were identified in the infected and noninfected males, including fatty acids, fatty acid methyl esters (FAMEs), n-alkanes, alcohols, sterols, and other organic compounds. The most abundant components of the cuticular and internal lipids of the insects were fatty acids. After exposure to C. coronatus, the cuticular lipids of the T. viridissima males contained 17 free fatty acids from C(8) to C(22), while the cuticular lipids of the noninfected insects contained only 15 fatty acids from C(12) to C(24). The cuticular and internal lipids of both the infected and the noninfected males also contained five FAMEs from C(15) to C(19), seven n-alkanes from C(25) to C(34), five alcohols from C(16) to C(25), five sterols, and the following six other organic compounds: azelaic acid, phenylacetic acid, glutaric acid, benzoic acid, sebacic acid, and glycerol. The compounds which were present only in the cuticular lipids of the infected males could be due to fungal infection.


Planning study of flattening filter free beams for volumetric modulated arc therapy in squamous cell carcinoma of the scalp.
Flattening filter free (FFF) beams show the potential for a higher dose rate and lower peripheral dose. We investigated the planning study of FFF beams with their role for volumetric modulated arc therapy (VMAT) in squamous cell carcinoma of the scalp. One patient with squamous cell carcinoma which had involvement of entire scalp was subjected to VMAT using TrueBeam linear accelerator. As it was a rare skin malignancy, CT data of 7 patients with brain tumors were also included in this study, and their entire scalps were outlined as target volumes. Three VMAT plans were employed with RapidArc form: two half-field full-arcs VMAT using 6 MV standard beams (HFF-VMAT-FF), eight half-field quarter-arcs VMAT using 6 MV standard beams (HFQ-VMAT-FF), and HFQ-VMAT using FFF beams (HFQ-VMAT-FFF). Prescribed dose was 25 × 2 Gy (50 Gy). Plan quality and efficiency were assessed for all plans. There were no statistically significant differences among the three VMAT plans in target volume coverage, conformity, and homogeneity. For HFQ-VMAT-FF plans, there was a significant decrease by 12.6% in the mean dose to the brain compared with HFF-VMAT-FF. By the use of FFF beams, the mean dose to brain in HFQ-VMAT-FFF plans was further decreased by 7.4% compared with HFQ-VMAT-FF. Beam delivery times were similar for each technique. The HFQ-VMAT-FF plans showed the superiority in dose distributions compared with HFF-VMAT-FF. HFQ-VMAT-FFF plans might provide further normal tissue sparing, particularly in the brain, showing their potential for radiation therapy in squamous cell carcinoma of the scalp.


Nanostructured Thermal Responsive Materials Synthesized by Soft Templating.
We capitalized herein the inherent tortuosity of bicontinuous microemulsion to conceive nanostructured drug-delivery devices. First, we show that it is possible to synthesize bicontinuous materials with continuous hydrophilic domains of the poly(N-isopropylacrylamide) (PNIPAM) network entangled with continuous hydrophobic polymer domains, with dual-phase continuity being imposed by the bicontinuous microemulsions used as a soft template. Particular attention is paid to the microemulsion formulations using a surfmer to preserve the one-to-one replication of the bicontinuous nanostructure after polymerization. These materials keep a volume phase transition with temperature that allows considering them as drug carriers for controlled release. PNIPAM, which plays the role of the active ingredient reservoir, is confined in the bicontinuous structure. As expected, the PNIPAM enclosure limits the surface area in contact with the releasing aqueous solution and thus slows down the desorption of aspirin, which is used as a model drug. The hydrophobic polymers play the role of in situ-created transport barriers without hindering it as all the loaded aspirin in this bicontinuous structure still remains available.


Measuring outcome after liver transplantation: a critical review.
As the number of liver transplantations performed around the world and the survival rates increase, attention is turning to the broad impact this procedure has on patients' quality of life (QOL), including their physical and psychosocial functioning and their perceived sense of well-being. There exists a small body of literature that examines the global effects of liver transplantation on QOL. The purpose of this article is to discuss the general framework used to assess QOL and to critically review the studies that have broadly examined QOL outcomes after liver transplantation. The reviewed studies used measures that led to broad assessment of the various domains of QOL. Although the instruments used to measure QOL in these studies are largely validated, there is significant heterogeneity in this literature in terms of the instruments used, leading to difficulties in making generalizable conclusions among the studies. Although limited by internal validity problems, the available data suggest improvement in QOL by liver transplantation. Additionally, a large recent study that used the Liver Transplant Database Quality of Life Questionnaire also reported a subset of patients in whom QOL seemed to worsen after liver transplantation. Knowledge of the factors related to QOL outcome after liver transplantation is important because it might allow development of new interventions that may have an impact on future allocation decisions.


Vitamin C intake and cardiovascular disease risk factors in persons with non-insulin-dependent diabetes mellitus. From the Insulin Resistance Atherosclerosis Study and the San Luis Valley Diabetes Study.
Persons with non-insulin-dependent diabetes mellitus (NIDDM) are at increased risk for cardiovascular disease, partly due to concomitant worsening of traditional risk factors including dyslipidemia and hypertension. Based on evidence from small, controlled clinical trials, we hypothesized that increased intake of vitamin C would be associated with improved cardiovascular disease (CVD) risk factor status among community-dwelling persons with NIDDM. In separate but parallel statistical analyses, hypotheses were evaluated among persons with NIDDM confirmed by WHO criteria from the Insulin Resistance Atherosclerosis Study (IRAS, n = 520) and from the San Luis Valley Diabetes Study (SLVDS, n = 422). For IRAS, diet and vitamin supplement use was assessed by food frequency interview and for SLVDS, by 24-hr dietary recall interview. Mean vitamin C intake (mg/day) was 275 for IRAS and 133 for SLVDS, including supplements. In cross-sectional regression models from each data set, vitamin C intake was not associated with systolic or diastolic blood pressure nor with HDL-C, LDL-C, or triglycerides (P values > 0.10; adjusted for calories, demographic and lifestyle variables, obesity, diabetes duration, and medications). In prospective analyses including 285 SLVDS participants, baseline vitamin C intake was not related to any of these CVD risk factors measured an average of 4 years later nor to change in CVD risk factor status during the follow-up period. We conclude that, across a wide range of intake, vitamin C does not appear to be associated with improved CVD risk factor status among community-dwelling persons with diabetes.


Fetal polyuria and hydramnios associated with Bartter's syndrome.
The case of a woman with recurrent hydramnios in three pregnancies, from which the only surviving infant was later found to have Bartter's syndrome, is described. Analysis of electrolytes, renin activity, and aldosterone levels in amniotic fluid from this pregnancy are presented. The finding of maternal hydramnios in the present and 12 other reported cases of Bartter's syndrome suggests that increased fetal voiding is the most likely causative factor in the development of increased amniotic fluid volume. Early onset hydramnios might signify Bartter's syndrome in the offspring in families with an index case. In cases of hydramnios of unknown etiology, appropriate investigations might lead to early diagnosis and treatment of Bartter's syndrome.


Effect of guar on amino acid absorption and the blood glucose, insulin, C-peptide and glucagon responses to jejunal amino acid and glucose perfusion in man.
The effect of guar on the plasma glycine response to a glycine drink was measured in six normal subjects. Guar reduced the increment in plasma glycine over the first 60 min and also reduced the total integrated plasma glycine response. The effect of guar on the peripheral blood glucose, insulin, C-peptide and glucagon responses following jejunal amino acid or glucose perfusion was measured in nine normal subjects. Guar reduced the blood glucose, insulin and C-peptide responses to the glucose perfusion and reduced the insulin and C-peptide responses to the amino acid perfusion. The addition of guar did not alter C-peptide:insulin ratios following either glucose or amino acid administration. It is concluded that guar reduces the rate of amino acid absorption and of amino acid-stimulated insulin release. Modulation of intestinal mechanisms is sufficient to mediate the latter effect. The reduction in peripheral blood insulin levels caused by guar is not associated with a change in hepatic insulin extraction.


Self-similar regimes of turbulence in weakly coupled plasmas under compression.
Turbulence in weakly coupled plasmas under compression can experience a sudden dissipation of kinetic energy due to the abrupt growth of the viscosity coefficient governed by the temperature increase. We investigate in detail this phenomenon by considering a turbulent velocity field obeying the incompressible Navier-Stokes equations with a source term resulting from the mean velocity. The system can be simplified by a nonlinear change of variable, and then solved using both highly resolved direct numerical simulations and a spectral model based on the eddy-damped quasinormal Markovian closure. The model allows us to explore a wide range of initial Reynolds and compression numbers, beyond the reach of simulations, and thus permits us to evidence the presence of a nonlinear cascade phase. We find self-similarity of intermediate regimes as well as of the final decay of turbulence, and we demonstrate the importance of initial distribution of energy at large scales. This effect can explain the global sensitivity of the flow dynamics to initial conditions, which we also illustrate with simulations of compressed homogeneous isotropic turbulence and of imploding spherical turbulent layers relevant to inertial confinement fusion.


Modulator-Controlled Synthesis of Microporous STA-26, an Interpenetrated 8,3-Connected Zirconium MOF with the the-i Topology, and its Reversible Lattice Shift.
A fully interpenetrated 8,3-connected zirconium MOF with the the-i topology type, STA-26 (St Andrews porous material-26), has been prepared using the 4,4',4"-(2,4,6-trimethylbenzene-1,3,5-triyl)tribenzoate (TMTB) tritopic linker with formic acid as a modulating agent. In the as-prepared form STA-26 possesses Im3‾ m symmetry compared with the Pm3‾ m symmetry of the non-interpenetrated analogue, NU-1200, prepared using benzoic acid as a modulator. Upon removal of residual solvent there is a shift between the interpenetrating lattices and a resultant symmetry change to Cmcm which is fully reversible. This is observed by X-ray diffraction and 13 C MAS NMR is also found to be remarkably sensitive to the structural transition. Furthermore, heating STA-26(Zr) in vacuum dehydroxylates the Zr6 nodes leaving coordinatively unsaturated Zr4+ sites, as shown by IR spectroscopy using CO and CD3 CN as probe molecules. Nitrogen adsorption at 77 K together with grand canonical Monte Carlo simulations confirms a microporous, fully interpenetrated, structure with pore volume 0.53 cm3 g-1 while CO2 adsorption at 196 K reaches 300 cm3 STP g-1 at 1 bar. While the pore volume is smaller than that of its non-interpenetrated mesoporous analogue, interpenetration makes the structure more stable to moisture adsorption and introduces shape selectivity in adsorption.


Infectious and Autoimmune Causes of Encephalitis in Children.
Encephalitis can result in neurologic morbidity and mortality in children. Newly recognized infectious and noninfectious causes of encephalitis have become increasingly important over the past decade. We retrospectively reviewed medical records from pediatric patients in Houston diagnosed with encephalitis in both an urban and rural catchment area between 2010 and 2017. We conducted an investigation to understand the etiology, clinical characteristics, and diagnostic testing practices in this population. We evaluated 231 patients who met the case definition of encephalitis, among which 42% had no recognized etiology. Among those with an identified etiology, the most common were infectious (73; 31%), including viral (n = 51; 22%), with the most frequent being West Nile virus (WNV; n = 12), and bacterial (n = 19; 8%), with the most frequent being Bartonella henselae (n = 7). Among cases of autoimmune encephalitis (n = 60; 26%), the most frequent cause was anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis (n = 31). Autoimmune causes were seen more commonly in female (P < .01) patients. Testing for herpes simplex virus and enterovirus was nearly universal; testing for anti-NMDAR encephalitis, WNV, and Bartonella was less common. WNV was the most common infectious cause of encephalitis in our pediatric population despite lower testing frequency for WNV than herpes simplex virus or enterovirus. Increasing testing for anti-NMDAR encephalitis resulted in frequent identification of cases. Increased awareness and testing for WNV and Bartonella would likely result in more identified causes of pediatric encephalitis. Earlier etiologic diagnosis of encephalitides may lead to improve clinical outcomes.


Medical imagery in Maximus of Tyre's Orations.
Imagery is an overarching feature of Maximus of Tyre's Orations which has never been the subject of systematic investigation. This paper provides a starting point by focusing exclusively on medical imagery, one of the most pervasive and instrumental types of imagery in Maximus' work that has gone entirely unnoticed in the literature to date. This paper shows that Maximus uses medicine (especially its scientific basis and historical development), the physician (e.g. his skill, provision and sensitivity towards the patient), the body (its physiology and workings) and notions of health and disease with considerable diversity and creativity, in ways that make his examples stand out in relation to earlier (Platonic) or contemporary applications of the medical parallel. It argues that the use of the medical imagery in the pedagogical context in which Maximus' Orations were performed facilitated not just clarity but also concept formation and the shaping of a moral outlook as well as the familiarisation with the proper literary references and verbal and conceptual topoi for admission into the group of the educated elite. Another main thesis is that medical imagery valorises Maximus' philosophical status and his claims to Imperial-period acculturation, thus functioning as a trademark for the rhetorical philosophy he wished to promote.


Partial ozonation pre-treatment for sludge solubilization and simultaneous degradation of bisphenol A: quantification studies.
Ozonation pre-treatment was investigated for the enhancement of sludge solids and organic matter solubilization and simultaneous degradation of bisphenol A (BPA), an endocrine disruptor compound from wastewater sludge (WWS). The ultrafast method (15 s per sample) used for the analysis of BPA in WWS is based on Laser Diode Thermal Desorption/Atmospheric Pressure Chemical Ionization coupled to tandem Mass Spectrometry. The statistical methods used for optimization studies comprised the response surface method with fractional factorial designs and central composite designs. The ozonation pre-treatment process was carried out with four independent variables, namely WWS solids concentration (15-35 g l(-1)), pH (5-7), ozone dose (5-25 mg g(-1) SS) and ozonation time (10-30 min). It was observed that among all the variables studied, ozone dose had more significantly (probability (p) < 0.001) affected the efficiency of the ozonation pre-treatment by increasing sludge solids (suspended solids (SS) and volatile solids) solubilization and organic matter (soluble chemical oxygen demand and soluble organic carbon) increment and BPA degradation from WWS. During the optimization process, it was found that higher BPA degradation (100%) could be obtained with 24 g l(-1) SS, 6.23 pH with an ozone dose of 26.14 mg g(-1) SS for 16.47 min ozonation time. The higher ozone dose used in this study was observed to be cost effective on the basis of solids and organic matter solubilization and degradation of BPA.


Continuous-data diagnostic tests for paratuberculosis as a multistage disease.
We devised a general method for interpretation of multistage diseases using continuous-data diagnostic tests. As an example, we used paratuberculosis as a multistage infection with 2 stages of infection as well as a noninfected state. Using data from a Danish research project, a fecal culture testing scheme was linked to an indirect ELISA and adjusted for covariates (parity, age at first calving, and days in milk). We used the log-transformed optical densities in a Bayesian network to obtain the probabilities for each of the 3 infection stages for a given optical density (adjusted for covariates). The strength of this approach was that the uncertainty associated with a test was imposed directly on the individual test result rather than aggregated into the population-based measures of test properties (i.e., sensitivity and specificity).


The curative effects of the traditional Chinese herbal medicine "Jinchuang ointment" on excisional wounds.
"Jinchuang ointment" is a traditional Chinese herbal medicine for external incised wounds. This herbal medicine has been successfully used to treat patients with diabetic foot ulcers and pressure sores in Taiwan for several decades. We previously examined its biological activities on cell-based in vitro assay platforms. Because some patients refused to use animal-derived ingredients ointment during our clinical practice, the efficacy of plant oil-based reconstituted "Jinchuang ointment" was also investigated. A porcine excisional wound model was established and used to evaluate its efficacy in vivo in this study. Besides, an unusual clinical case is also present. As judged from the wound appearance of animal studies on day 14 and the results of blood flow flux at the wound sites on day 28, "Jinchuang ointment" accelerated wound closure significantly better than the control group. The results from clinical treatment, histopathological evaluation, and the animal study showed that "Jinchung ointment" promotes wound healing significantly better than the control group. Also, sesame oil-reconstituted ointment can be a choice for patients who refuse to use lard-containing ointment.


Evaluation of HIV/STD prevention, care and support: an update on WHO's approaches.
Over the past decade only a limited number of public health initiatives have been subjected to systematic monitoring and evaluation and, in many instances, there is growing pressure to estimate which approaches work best for a given level of inputs in order to allocate resources effectively. However, evaluation is very often seen as punitive, and a change in perception is needed to allow evaluation to be owned by all stakeholders in public programs. In the field of HIV/AIDS prevention and care, the first difficulty is that many national AIDS programs lack clearly stated objectives and involve a wide variety of players. These players each have their own guidelines for project/program design, monitoring, and evaluation. The second difficulty relates to the fact that evaluation involves "multiple methods, multiple audiences, multiple funding sources, multiple perspectives, multiple paradigms, multiple roles, and multiple solutions to multiple problems" (Quinn Patton, 1986). To some people, evaluation calls for complex experimental studies while to others it means pausing at the end of an activity to sort out what went well and what went less successfully. This paper examines briefly some of the problems and challenges facing the evaluation of HIV prevention and care and summarizes the approaches adopted by the World Health Organization (WHO) to assist AIDS programs around the world in evaluating their initiatives. The paper also provides an update on the progress of developments, training, and implementation of these approaches.


Repercussions of SARS-CoV-2 infection and the pandemic on birth routes: a cross-sectional study.
To assess the repercussions of SARS-CoV-2 infection (suspected or confirmed) and the context of the pandemic on the birth route and humanized assistance during childbirth. Cross-sectional epidemiological study, nested within a cohort and comparative with the research "Birth in Belo Horizonte: Survey on Childbirth and Delivery".The medical records of three reference maternity hospitals in Belo Horizonte were assessed, with a final sample of 1,682 pregnant women, in the months of May, June and July 2020. A descriptive analysis was carried out, with absolute and relative frequency, and a comparative one, with a Pearson's chi-square test. It was observed that 2.02% of pregnant women were infected with SARS-CoV-2.Before the pandemic, out of a total of 390 pregnant women, 74.10% gave birth vaginally.During a pandemic, among infected women, 51.61% gave birth via cesarean section and 48,39% via vaginal delivery;among uninfected, 26.99% cesarean sections and 73.01% vaginaldeliveries. There was an increase in the percentage of cesarean sections and a possible influence of the pandemic on the rates of indication of cesarean sections at the time of admission to the maternity ward.


Evolving views of pectin biosynthesis.
Recent progress in the identification and characterization of pectin biosynthetic proteins and the discovery of pectin domain-containing proteoglycans are changing our view of how pectin, the most complex family of plant cell wall polysaccharides, is synthesized. The functional confirmation of four types of pectin biosynthetic glycosyltransferases, the identification of multiple putative pectin glycosyl- and methyltransferases, and the characteristics of the GAUT1:GAUT7 homogalacturonan biosynthetic complex with its novel mechanism for retaining catalytic subunits in the Golgi apparatus and its 12 putative interacting proteins are beginning to provide a framework for the pectin biosynthetic process. We propose two partially overlapping hypothetical and testable models for pectin synthesis: the consecutive glycosyltransferase model and the domain synthesis model.


Characterization of Haemophilus influenzae type b fimbriae.
We confirmed that the fimbriae of Haemophilus influenzae type b conferred hemagglutinating activity (HA) towards human erythrocytes, and erythrocytes of certain other species. Most (17/25) cerebrospinal fluid isolates lacked detectable HA on direct testing, but selective enrichment for fimbriation (f+) indicated that 22 of 25 strains could produce these surface structures. HA was unchanged from pH 4.5 to 9.5 and was not inhibited by mannose or certain other simple sugars. The HA titer of a suspension of three f+ strains was slightly decreased at 50 degrees C; HA was lost by heating at 60 degrees C for 3 min. Growth on a variety of solid and liquid media and under differing degrees of oxygenation did not change the HA titer of a suspension of three f+ strains. Fimbriation was not lost on repeated subculture. Wild-type fimbriated strains, and those derived by transformation, did not contain detectable plasmid DNA. Transformation of a strain lacking fimbriae to f+ was associated with the appearance of an outer membrane protein of 24 kilodaltons. This protein was purified from one strain to homogeneity on sodium dodecyl sulfate-polyacrylamide gel electrophoresis by selective detergent solubilization and ammonium sulfate fractionation. Colonization capacity was equivalent with an isogenic untypable strain lacking or possessing fimbriae. Fimbriae of type b H. influenzae possess characteristics similar to those structures on other gram-negative bacteria; their role in cell physiology or pathogenesis of invasive disease is unknown.


Preconditioning programs for feeder cattle.
Over two-thirds of American feeder cattle originate in herds of less than 50 cows, and over 40% are finished in fewer than 200 feedlots . Preconditioning programs first originated in the late 1960's but did not become popular for another 10 years. A dozen states now have fairly uniform programs, with requirements involving certificates and ear tags, prior ownership, preweaning, dehorning, castration, grub/lice treatment, deworming and various vaccinations. Preconditioning programs have been criticized as not cost-effective, but proponents cite superior postweaning weight gains, enhanced sales, improved management, more uniform calves, and decreased morbidity and mortality.


[Clinical investigation of three cases of pulmonary eosinophilic granuloma].
Patient 1: An 18-year-old woman was admitted to our hospital with pneumothorax. She had no history of smoking. Chest CT showed multiple cysts, and pulmonary eosinophilic granuloma was diagnosed by open lung biopsy. She recovered without therapy 3 months later and a chest CT taken at that time was normal. She began smoking, 3 years later, and bore two children. She is without recurrence after 8 years. Patient 2: A 23-year-old man was admitted to our hospital with pneumothorax. He had a smoking history (index = 180). Chest CT showed multiple cysts, and pulmonary eosinophilic granuloma was diagnosed by open lung biopsy. He stopped smoking and recovered without therapy one month later, and subsequently, his CT findings returned to normal. Two years later, he began smoking again, but has no relapse. Patient 3: A 21-year-old man was admitted to our hospital with pneumothorax. He had no history of smoking. A chest CT showed multiple cysts, and pulmonary eosinophilic granuloma was diagnosed by open lung biopsy. Diabetes insipidus was subsequently noted. Dyspnea persisted, and he recovered 4 months later after steroid treatment. He was without relapse 2 years later but the multiple cysts remained. We report three cases of pulmonary eosinophilic granuloma, and discuss their pertinent clinical features.


[Alcohol intake and stroke in Eastern Asian men:a systemic review and meta-analysis of 17 prospective cohort studies].
To assess the dose-response relationship between alcohol intake and relative risk of stroke and all-cause mortality among Eastern Asian men. Potential prospective cohort studies were retrieved by searching Pubmed (1966 - 2000), OVID (1980 - 2009), Embase (1980 - 2009) and ISI Web of Knowledge (1986 - 2009) using Medical Subject Headings: alcohol drinking, ethanol, stroke, cerebrovascular disease, mortality, etc; and Koreans or Japanese or Chinese. From the relevant retrieved reports, 17 prospective cohort studies fulfilling the criteria were included into the study. Information on study design, participant characteristics, amount of alcohol intake, stroke and/or all-cause mortality outcomes, control for potential confounding factors and risk estimates was abstracted by a standardized protocol. For each study, relative risk (RR) and 95% confidence interval (CI) were extracted and pooled with either a fixed or random effect model according to the results of the test of heterogeneity. As data available for women were too limited to be included into our meta-analysis, this study focused on male subjects, ranging from 1322 to 108 461 subjects among these 17 cohort studies. Compared with nondrinkers, the RRs of ischemic stroke for those drinking alcohol ≤ 20, 21 - 40, 41 - 60, > 60 g/d, were 0.85 (0.78 - 0.93, P = 0.0002), 0.94 (0.79 - 1.11, P = 0.46), 1.08 (0.86 - 1.37, P = 0.50) and 1.24 (0.96 - 1.59, P = 0.10) respectively. Similarly, RRs of hemorrhagic stroke were 0.92 (0.75 - 1.12, P = 0.46), 1.11 (0.96 - 1.28, P = 0.17), 1.20 (0.92 - 1.56, P = 0.18) and 1.74 (1.32 - 2.28, P < 0.01); and those of all-cause mortality were 0.83 (0.75 - 0.91, P = 0.01), 0.93 (0.87 - 0.99, P = 0.03), 1.01 (0.95 - 1.07, P = 0.86) and 1.32 (1.29 - 1.36, P < 0.01) respectively. In Eastern Asian men, light alcohol intake (≤ 20 g/d) is associated with a lowered risk of ischemic stroke whereas heavy alcohol intake is associated with an elevated risk of stroke, particularly hemorrhagic stroke and all-cause mortality.


Selected adverse reactions of D-penicillamine.
Selected adverse reactions of penicillamine encountered in our clinic since 1975 are described. They include: proteinuria (26 cases), lupus erythematosus (six cases), myasthenia gravis (two cases), pemphigus (three cases), obliterative bronchiolitis (two cases) and obstructive jaundice (one case).


Fifteen years of Nucleic Acid Testing in France: Results and lessons.
Of the 40 million donations screened with Nucleic acid testing (NAT) between July 2001 and December 2015 in France, 20 HIV-positive, 13 HCV-positive and 17 HBV (HBV-NAT was initiated in 2005 and extended to the whole country in 2010) donations were discarded thanks to NAT. The main benefit in terms of discarded donations is related to HBV with a yield of 0.88 per million donations, which is 12.5 and 1.8 times higher than for HCV and HIV respectively. The main risk factor found in these donors during the post donation interview was having sex with men for males (n=11, all repeat blood donors), having a partner HCV positive (n=6) or at-risk partner (originated from endemic area or HBV positive) for HBV (n=8) for HIV, HCV and HBV, respectively. Although the mean viral load was high for HIV (5.6 log copies/mL) and HCV (7 log IU/mL), HBV cases show low level of DNA (1.8 log IU/mL) demonstrating the need of a highly sensitive NAT assay. Overall, the clinical benefit for recipients remains those related to the prevention of HIV contaminations since HCV avoided transmissions are extremely rare (only one case in the last 5 years thanks to NAT) and the potential infectivity of HBV-NAT only positive cases is questionable due to the low level of HBV DNA and the presence of anti-HBs in more than a half of DNA positive/HBsAg and anti-HBc negative donors.


Characteristics of urban natural areas influencing winter bird use in southern Ontario, Canada.
Characteristics of urban natural areas and surrounding landscapes were identified that best explain winter bird use for 28 urban natural areas in southern Ontario, Canada. The research confirms for winter birds the importance of area (size) and natural vegetation, rather than managed, horticultural parkland, within urban natural areas as well as percent urban land use and natural habitat in surrounding landscapes. Alien bird density and percent ground feeding species increased with percent surrounding urban land use. Higher percent forest cover was associated with higher percentages of forest, bark feeding, small (<20 g) and insectivorous species. Natural area size (ha) was related to higher species richness, lower evenness and higher percentages of insectivorous, forest interior, area-sensitive, upper canopy, bark feeding, and non-resident species. Higher number of habitat types within natural areas and percent natural habitat in surrounding landscapes were also associated with higher species richness. Common, resident bird species dominated small areas (<6.5 ha), while less common non-residents increased with area, indicative of a nested distribution. Areas at least 6.5 ha and more generally >20 ha start to support some area-sensitive species. Areas similar to rural forests had >25% insectivores, >25% forest interior species, >25% small species, and <5% alien species. Indicator species separated urban natural areas from rural habitats and ordination placed urban natural areas along a gradient between urban development and undisturbed, rural forests. More attention is needed on issues of winter bird conservation in urban landscapes.


Postoperative mortality risk assessment in colorectal cancer: development and validation of a clinical prediction model using data from the Dutch ColoRectal Audit.
As the outcome of modern colorectal cancer (CRC) surgery has significantly improved over the years, however, renewed and adequate risk stratification for mortality is important to identify high-risk patients. This population-based study was conducted to analyse postoperative outcomes in patients with CRC and to create a risk model for 30-day mortality. Data from the Dutch Colorectal Audit were used to assess differences in postoperative outcomes (30-day mortality, hospital stay, blood transfusion, postoperative complications) in patients with CRC treated from 2009 to 2017. Time trends were analysed. Clinical variables were retrieved (including stage, age, sex, BMI, ASA grade, tumour location, timing, surgical approach) and a prediction model with multivariable regression was computed for 30-day mortality using data from 2009 to 2014. The predictive performance of the model was tested among a validation cohort of patients treated between 2015 and 2017. The prediction model was obtained using data from 51 484 patients and the validation cohort consisted of 32 926 patients. Trends of decreased length of postoperative hospital stay and blood transfusions were found over the years. In stage I-III, postoperative complications declined from 34.3 per cent to 29.0 per cent (P < 0.001) over time, whereas in stage IV complications increased from 35.6 per cent to 39.5 per cent (P = 0.010). Mortality decreased in stage I-III from 3.0 per cent to 1.4 per cent (P < 0.001) and in stage IV from 7.6 per cent to 2.9 per cent (P < 0.001). Eight factors, including stage, age, sex, BMI, ASA grade, tumour location, timing, and surgical approach were included in a 30-day mortality prediction model. The results on the validation cohort documented a concordance C statistic of 0.82 (95 per cent c.i. 0.80 to 0.83) for the prediction model, indicating good discriminative ability. Postoperative outcome improved in all stages of CRC surgery in the Netherlands. The developed model accurately predicts postoperative mortality risk and is clinically valuable for decision-making.


[Corneal radius of curvature among people with myopia].
To determine the behaviour of the radius of corneal curvature among people with myopia. A total of 167 people with myopia (117 women and 50 men) aged 12 and 51, were examined. The average of age was 24. Routine ophthalmological examinations as well as keratometry were carried out. The data was analysed using the coefficient of rang Spearman's correlation and the coefficient of linear Pearson's correlation. A positive correlation was found between the length of an average of corneal curvature radius and myopia progress (P < 0.007). Any correlation between the age of the people with low, medium, and high myopia and the corneal curvature radius length was not observed. (1) In the course of myopia the average of corneal curvature radius is reduced. (2) The length of the average of corneal curvature radius does not depend on the age of people with myopia.


Region-specific effects of Scrapper on the abundance of glutamate and gamma-aminobutyric acid in the mouse brain.
The brain consists of various areas with anatomical features. Neurons communicate with one another via excitatory or inhibitory synaptic transmission. Altered abundance of neurotransmitters, including glutamate and gamma-aminobutyric acid (GABA), in specific brain regions is closely involved in severe neurological diseases, such as schizophrenia and obsessive-compulsive disorder. SCRAPPER, a ubiquitin E3 ligase, regulates synaptic transmission. Scrapper gene deficiency results in defective neurotransmission due to excessive secretion of neurotransmitters. The present study employed matrix-assisted laser desorption/ionization imaging mass spectrometry to analyze the abundance of amino acid neurotransmitters in Scrapper knockout (SCR-KO) mice. SCR-KO mice exhibited significantly increased glutamate levels in the isocortex (CTX), corpus callosum (CC), thalamus (TH), midbrain (MB), cerebellar cortex (CBX), and caudoputamen (CP) and increased GABA levels in the CTX, CC, TH, MB, CBX and hypothalamus (HY) compared with wild-type mice. These findings indicate that Scrapper deficiency leads to upregulated glutamate and GABA levels in multiple regions. Our results show a differential, region-specific effect of Scrapper on the abundance of glutamate and GABA.


Low prevalence of osteoporosis treatment in patients with recurrent major osteoporotic fracture.
The majority of patients do not receive anti-osteoporotic treatment following a major osteoporotic fracture, despite the guidelines and the availability of effective anti-osteoporotic treatments. The fight against factors limiting the diagnosis and treatment of osteoporosis should become a priority to improve secondary prevention after an initial osteoporotic fracture. Despite the availability of effective anti-osteoporotic treatments, osteoporosis management is currently insufficient. The main objective of this study was to assess the prevalence of anti-osteoporotic treatments introduced after an initial prior major osteoporotic fracture during hospitalization for recurring fractures. We conducted an observational, cross-sectional, bicentric study that included all patients aged over 50 years who were hospitalized or seen in consultation for major osteoporotic fracture. One hundred twenty-eight out of two hundred four (62.7%) patients had a past history of major osteoporotic fracture and therefore had an indication of treatment based on guidelines. Among these patients, only 43/128 (33.5%) had received anti-osteoporotic treatment as secondary prevention after the initial fracture. The main causes of non-prescription identified were the attending physicians' ignorance of the indication of treatment (n = 30; 35.3%), ignorance of the fracture (n = 17; 20%), and comorbidities (n = 12; 14.1%). The failure to introduce treatment was associated with the presence of comorbidities with a Charlson Comorbidity Index ≥6 (OR = 0.34 [0.16-0.73], p < 0.05), dementia (OR = 0.23 [0.08-0.72], p < 0.05), and past history of proximal femur fracture (OR = 0.20 [0.04-0.91], p < 0.05). Two thirds of patients with a past history of major osteoporotic fracture presenting with a new fracture were not treated. The main reason for lack of treatment seems to stem from the incorrect assessment of the patient's fracture risk. Although major osteoporotic fracture leads to an increased risk of mortality and requires treatment, the significance of patient comorbidities was an independent risk factor leading to non-treatment.


The Androgen Receptor Supports Tumor Progression After the Loss of Ovarian Function in a Preclinical Model of Obesity and Breast Cancer.
The androgen receptor (AR) has context-dependent roles in breast cancer growth and progression. Overall, high tumor AR levels predict a favorable patient outcome, but several studies have established a tumor promotional role for AR, particularly in supporting the growth of estrogen receptor positive (ER-positive) breast cancers after endocrine therapy. Our previous studies have demonstrated that obesity promotes mammary tumor progression after ovariectomy (OVX) in a rat model of postmenopausal breast cancer. Here, we investigated a potential role for AR in obesity-associated post-OVX mammary tumor progression following ovarian estrogen loss. In this model, we found that obese but not lean rats had nuclear localized AR in tumors that progressed 3 weeks after OVX, compared to those that regressed. AR nuclear localization is consistent with activation of AR-dependent transcription. Longer-term studies (8 weeks post-OVX) showed that AR nuclear localization and expression were maintained in tumors that had progressed, but AR expression was nearly lost in tumors that were regressing. The anti-androgen enzalutamide effectively blocked tumor progression in obese rats by promoting tumor necrosis and also prevented the formation of new tumors after OVX. Neither circulating nor mammary adipose tissue levels of the AR ligand testosterone were elevated in obese compared to lean rats; however, IL-6, which we previously reported to be higher in plasma from obese versus lean rats, sensitized breast cancer cells to low levels of testosterone. Our study demonstrates that, in the context of obesity, AR plays a role in driving ER-positive mammary tumor progression in an environment of low estrogen availability, and that circulating factors unique to the obese host, including IL-6, may influence how cancer cells respond to steroid hormones.


Hif1α-dependent hypoxia signaling contributes to the survival of deep-layer neurons and cortex formation in a mouse model.
Hypoxia-inducible factor 1 α (Hif1α) plays a crucial role in brain development. To study the function of Hif1α in early brain development, we generated neuroepithelial cell-specific Hif1α-knockout mice. Hif1α-knockout mice died soon after birth; these mice exhibited an abnormal head shape, indicating the presence of brain defects. Morphological analysis revealed that Hif1α ablation reduced the overall size of the brain, especially affecting the telencephalon. Neuronal apoptosis predominantly occurred in deep-layer neurons, consequently the alignment of cortical layers was severely disorganized in Hif1α knockout mice. Furthermore, we demonstrated that Vegf signaling contributes to the survival of deep-layer neurons as a downstream effector of Hif1α-dependent hypoxia signaling. Taken together, our findings demonstrate that Hif1α plays a critical role in the early stages of telencephalon development.


Registration status and outcome reporting of trials published in core headache medicine journals.
To evaluate randomized controlled trial (RCT) registration and outcome reporting compliance in core headache medicine journals. We identified RCTs published in core journals (Headache, Cephalalgia, and the Journal of Headache and Pain) from 2005 through 2014. We searched articles for trial registration numbers, which were verified in the corresponding trial registry. We categorized trial funding sources as industry, academic, government, or mixed. We contacted corresponding authors to assess reasons for nonregistration. We evaluated whether primary outcomes in trial registries matched those in corresponding publications. The journals published 225 RCTs over the study period. Fifty-eight of 225 (26%) reported a trial registration number in the article that could be linked to a corresponding registry entry. Trial registration rates increased over the 9 years of the study. Forty-six of 118 (39%) of industry-funded studies were registered compared with 27% of academic and 0% of government-funded studies. Only 5% of RCTs were prospectively registered, reported primary outcomes identical to those in the trial registry, and did not report unacknowledged post hoc outcomes. The most common reason for nonregistration was lack of awareness. Only about a quarter of the articles published in the core headache medicine journals are compliant with trial registration, but compliance has increased over time. Selective reporting of outcomes remains a problem, and very few trials met all 3 reporting standards assessed in this study. Efforts to improve the quality of trial reporting in the headache literature should continue.


Effect of Attachment Type on Denture Strain in Maxillary Implant Overdentures: Part 1. Overdenture with Palate.
This study examined the effects of attachments on strain in maxillary implant overdentures supported by two or four implants. A maxillary edentulous model with implants inserted into anterior, premolar, and molar areas was fabricated, and three types of unsplinted attachments-ball, locator, and magnet-were set on the implants distributed under various conditions. Maxillary experimental dentures were fabricated, and two strain gauges were attached at the anterior midline on the labial and palatal sides. A vertical occlusal load of 98 N was applied and shear strain of the dentures was measured. On both sides, magnet attachments resulted in the lowest shear strain, while ball attachments resulted in the highest shear strain under most conditions. However, differences in shear strain among the three attachment types were not significant when supported by four implants, especially molar implants. Shear strain of the maxillary implant overdenture was lowest when using magnet attachments. Magnet attachments mounted on four implants are recommended to prevent denture complications when using maxillary implant overdentures.


Problematic dyadic interaction among toddlers and their polydrug-cocaine-using mothers.
Dyadic interactions between 84 at-risk toddlers and their nondrug-, polydrug-non-cocaine-, or polydrug-cocaine-using mothers were examined during unstructured play. Coded videotaped behaviors revealed two maternal constructs (interactive competence, maladaptive engagement) and three toddler constructs (responsiveness, active positive initiation, play). Cocaine-using mothers displayed more maladaptive engagement than did prenatal nondrug users; however, poorer interactive competence further distinguished them from polydrug-but-noncocaine users. Toddlers of cocaine-using mothers displayed less responsiveness and positive initiation than non-drug-group peers; however, these behaviors did not reliably differ from polydrug-non-cocaine counterparts. Play interest remained relatively similar across groups. Results suggest that difficulties in social interaction appear to continue among cocaine-using mothers during dyadic exchanges with their offspring in the second year; however, toddler deficits do not appear to be greater than those experienced by polydrug-non-cocaine counterparts.


Distinct relationship between HLA-DR genes and intractability of ulcerative colitis.
To explain the correlation between HLA class II genes and the intractability of ulcerative colitis (UC), DR genotyping and clinical analysis were performed for patients with UC. HLA-DRB types and HLA-DR2 subtypes of 45 patients with UC in our hospital were determined using molecular genotyping in combination with sequence-specific oligonucleotide hybridization by polymerase chain reactions. The extent of involvement, clinical course, and treatment were studied to evaluate the intractability of UC. The gene frequency of DRB1*1502 in 18 patients with total colitis (0.444) was significantly higher than the group with left-sided colitis and proctitis (0.148; p < 0.05). In addition, DRw11 and DR2 increased significantly in the group including 18 cases with total colitis. In the 11 patients with total colectomy there were no cases with DRB1*1501, whereas 34 patients without operation included 12 genes of DRB1*1501 (p < 0.05). In addition, DRw11 increased significantly in the group with total colectomy compared to the group without operation (p < 0.05). When comparing between patients with and without intractability (defined based on the Japanese definition), DRB1*1502 and DRw11 were found more frequently in intractable UC patients (p < 0.01), whereas DRB1*1501 increased significantly in cases without intractability (p < 0.05). DRB1*1502 or DRw11 have a probability of being closely related to the intractability of UC. In addition, patients with UC possessing DRB1*1501 have a lower probability of their cases leading to intractable UC. Thus, we believe there are unknown genes present that encode the intractability of UC.


To Tube or Not to Tube? The Role of Intubation during Stroke Thrombectomy.
In the 10 years since the FDA first cleared the use of endovascular devices for the treatment of acute stroke, definitive evidence that such therapy improves outcomes remains lacking. The decision to intubate patients undergoing stroke thrombectomy impacts multiple variables that may influence outcomes after stroke. Three main areas where intubation may deleteriously affect acute stroke management include the introduction of delays in revascularization, fluctuations in peri-procedural blood pressure, and hypocapnia, resulting in cerebral vasoconstriction. In this mini-review, we discuss the evidence supporting these limitations of intubation during stroke thrombectomy and encourage neurohospitalists, neurocritical care specialists, and neurointerventionalists to carefully consider the decision to intubate during thrombectomy and provide strategies to avoid potential complications associated with its use in acute stroke.


Multiphysics and Thermal Response Models to Improve Accuracy of Local Temperature Estimation in Rat Cortex under Microwave Exposure.
The rapid development of wireless technology has led to widespread concerns regarding adverse human health effects caused by exposure to electromagnetic fields. Temperature elevation in biological bodies is an important factor that can adversely affect health. A thermophysiological model is desired to quantify microwave (MW) induced temperature elevations. In this study, parameters related to thermophysiological responses for MW exposures were estimated using an electromagnetic-thermodynamics simulation technique. To the authors' knowledge, this is the first study in which parameters related to regional cerebral blood flow in a rat model were extracted at a high degree of accuracy through experimental measurements for localized MW exposure at frequencies exceeding 6 GHz. The findings indicate that the improved modeling parameters yield computed results that match well with the measured quantities during and after exposure in rats. It is expected that the computational model will be helpful in estimating the temperature elevation in the rat brain at multiple observation points (that are difficult to measure simultaneously) and in explaining the physiological changes in the local cortex region.


Stacking-Dependent Electrical Transport in a Colloidal CdSe Nanoplatelet Thin-Film Transistor.
Here, we report an exceptional feature of the one-dimensional threadlike assemblies of a four-monolayer colloidal CdSe nanoplatelet (NPL)-based thin-film transistor. A series of different lengths of threads (200-1200 nm) was used as an active n channel in thin-film transistors (TFTs) to understand the change in mobility with the length of the threads. The film with the longest threads shows the highest conductivity of ∼12 S/cm and electron mobility of ∼14.3 cm2 V-1 s-1 for an applied gate voltage of 2 V. The mobility trends with the length seem to be driven mostly by the lower defects in threads, where the loss of electron hopping is less. Furthermore, our results show the mobility trends in stacking-dependent CdSe NPL threads and provide a new insight into fabricating high-mobility TFTs with the use of colloidal CdSe NPLs.


Remaking the future: contemplating a life with chronic widespread pain.
This paper reports findings from a larger study that aimed to explore how people with chronic widespread pain experience, understand and make meaning of their 'condition', and attempt to influence or exert control over their pain. This included an exploration of sufferers' understanding of the past and future as well as of their present situation. A combination of data generation methods was used, including lifegrid interviews, diaries and diary interviews, with eight people with chronic widespread pain. Five family members also participated in interviews. Analytical methods were based on interpretative phenomenological analysis (IPA). With regard to their views about the future, participants could be categorized into those who were 'optimistic' ('things can only get better'), those who were pessimistic ('things will get worse'), and those who were overwhelmed with uncertainty about the future. Uncertainty was a dominant feature in all the accounts of the future. The pervading uncertainty of chronic widespread pain, in which there is no framework for the trajectory of the condition, affects perceptions of the future and makes planning for the future difficult. The findings also raise the question of how this makes chronic widespread pain different from other chronic conditions in terms of understanding of chronicity, time and future, and hence 'acceptance'.


Induction of TAp73 by platinum-based compounds to overcome drug resistance in p53 dysfunctional chronic lymphocytic leukemia.
In chronic lymphocytic leukemia (CLL), strategies to overcome drug resistance due to p53 dysfunction are highly needed. Platinum-based compounds such as cisplatinum (CDDP) are active in fludarabine-refractory CLL through a largely unknown mechanism. We analyzed the mechanism of action of CDDP in the context of p53 dysfunctionality. In vitro treatment with CDDP did not induce death in quiescent CLL cells, but did induce apoptosis in CD40-ligand (and CpG) stimulated and proliferating cells, irrespective of p53 function. In the p53 dysfunctional prolymphocytic cell-line MEC1, CDDP treatment resulted in apoptosis, cell cycle arrest and ABL1-dependent expression of TAp73, CDKN1A, PUMA and BID. TAp73 RNA-interference decreased sensitivity to CDDP. Finally, both in vitro stimulated CLL cells and lymph node (LN) derived CLL cells showed increased TAp73 expression in comparison with quiescent peripheral blood derived cells. Activity of CDDP may therefore be mediated by TAp73, especially in the context of activation such as occurs in the LN microenvironment.


Comparison of lignin deposition in three ectopic lignification mutants.
The Arabidopsis thaliana mutants de-etiolated3 (det3), pom-pom1 (pom1) and ectopic lignification1 (eli1) all deposit lignins in cells where these polymers would not normally be found. Comparison of these mutants provides an opportunity to determine if the shared mutant phenotype arose by perturbing a common regulatory mechanism in each of the mutants. The mutants were compared using a combination of genetics, histochemistry, chemical profiling, transcript profiling using both Northern blots and microarrays, and bioinformatics. The subset of cells that ectopically lignified was shared between all three mutants, but clear differences in cell wall chemistry were evident between the mutants. Northern blot analysis of lignin biosynthetic genes over diurnal and circadian cycles revealed that transcript abundance of several key genes was clearly altered in all three mutants. Microarray analysis suggests that changes in the expression of specific members of the R2R3-MYB and Dof transcription factor families may contribute to the ectopic lignification phenotypes. This comparative analysis provides a suite of hypotheses that can be tested to examine the control of lignin biosynthesis.


Prelamination of the Anterolateral Thigh Flap With a Fibula Graft to Successfully Reconstruct a Mandibular Defect.
Flap prelamination is the process whereby a complex 3- dimensional construct is fashioned in a staged manner. We present a case whereby the tissues of the anterolateral thigh, nourished by perforators of the descending branch of the lateral circumflex femoral artery, were prelaminated with a fibula in the setting of salvage head and neck reconstruction. With a paucity of recipient vessels in the neck and a previous failed free fibula transfer secondary to osteoradionecrosis, a fibula was implanted into a suprafascial pocket created in the anterolateral thigh. This was allowed to pick up a blood supply from this rich vascular bed and mature over a period of 3 weeks before being transferred with the anterolateral thigh tissues as a prelaminated osteocutaneous composite free flap. A bone scan performed both before and after transfer confirmed uptake of radionucleotide by the fibula suggesting neovascularization. The composite mandibular defect was successfully reconstructed using this technique, and we believe this could represent a new strategy in the setting of salvage head and neck surgery.


Pathway classification of TCA cycle.
The structural analysis of large metabolic networks exhibits a combinatorial explosion of elementary modes. A new method of classification has been developed [called aggregation around common motif (ACoM)], which groups elementary modes into classes with similar substructures. This method is applied to the tricarboxylic acid cycle and metabolite carriers. The analysis of this network evidences a great number of elementary flux modes (204) despite the low number of reactions (23). The ACoM is used to class these elementary modes in a low number of sets (8) with biological meanings.


Increased levels of (2'-5')oligo(A) polymerase activity in human lymphoblastoid cells treated with glucocorticoids.
An enzymatic activity that synthesizes (2'-5')-oligo(A) from ATP is induced in animal cells treated with interferon. This activity, designated (2'-5')A polymerase, is also elevated in human lymphoblastoid Daudi and Raji cells treated with hydrocortisone. The polymerase activity increases significantly after 24 hr of treatment and declines when hydrocortisone is removed from the culture medium. The product of the enzyme prepared from hydrocortisone-treated cells is indistinguishable from (2'-5')oligo(A) synthesized with polymerase of interferon-treated cells either by an endonuclease activation assay or by chromatographic analysis. The increase in (2'-5')A polymerase is not mediated by secretion of interferon by hydrocortisone-treated cells; less than 1 unit of interferon per ml is present in the culture medium during treatment with this glucocorticoid hormone. Moreover, this increase is related to the concentration of hydrocortisone in the culture medium and is inhibited by the addition of cortexolone. This steroid interferes with the interaction between glucocorticoid hormones and their receptor. Cortexolone has no effect, however, on the induction of (2'-5')A polymerase by interferon. The synthetic glucocorticoid dexamethasone also increases the polymerase activity. Experiments with inhibitors show that such an increase requires RNA and protein synthesis.


Colitis cystica profunda lokalisata.
A 33-year-old man had a three-year history of ulcerative colitis. After 14 months of treatment he developed localized colitis cystica profunda mimicing a stenosating cancer of the rectum. The process developed over a short period. The diagnosis is based on a histological examination revealing benign submucosal cysts lined by columnar epithelium. A conservative surgical attitude is recommended.


Comparing Choice and Partnership Approach assumptions to Child and Adolescent Mental Health Services in NHS Greater Glasgow and Clyde.
The purpose of this paper is to compare NHS Greater Glasgow and Clyde (NHSGGC) Child and Adolescent Mental Health Service (CAMHS) activity data over a one-year period to the Choice and Partnership Approach (CAPA) demand and capacity model assumptions, providing an evaluation of CAPA model implementation and its effects on actual demand and capacity of the service. Three assumptions within the CAPA model are tested against activity data extracted from the patient management system. Analysis by patient record assesses the number of appointments the patients received and the patients' journey from assessment to treatment. A combination of community CAMHS data are combined to compare actual activity against assumed capacity required to meet demand according to the CAPA model. Tested against an audit of 2,896 patient records, CAMHS average 7.76 core appointments per patient compared to the CAPA assumption of 7.5 appointments at a 0 per cent DNA rate. The second CAPA assumption states that 66 per cent of assessments will result in treatment, compared to 73.55 per cent in NHSGGC CAMHS. Finally, the workforce model in CAMHS has clinical capacity to meet demand according to the CAPA assumption of weekly accepted referral rates not exceeding the number of clinical whole time equivalent. The data allow for identification of inefficiencies within CAMHS and highlights how capacity can be increased, without increasing budgets, to meet a rising clinical demand. The results allow managers and clinicians to improve job planning to ensure more children and young people have quick access to services.


[Assisted peritoneal dialysis].
Peritoneal dialysis (PD) has a prevalence in Italy that does not exceed 10% of patients in substitution treatment. Among the barriers, which hinder access to DP, the lack of patient autonomy or family support has great importance. In 2012 in Lombardy, the lack of support has prevented 155 new patients to use DP and has forced 17 to stop it. According to the Italian Census of 2012, made by the Peritoneal Dialysis Study Group, Assisted DP involved the 24.5% of patients in 2010. In these cases, the caregiver was a family member in 80.8% of cases, a carer in 12.4%, a homecare nurse in 2.5% and the retirement home staff in 3.9%. In Italy, several regional Governments have sought to encourage home dialysis with economic contributions to the patient or the family. However, so far, none of these interventions has managed to increase the use of DP. In January 2004, we started a program of Assisted PD, using health worker as caregiver, in agreement with ASL Milano and ICP Milano Hospital. In the first 6 months of activity we treated 4 patients, 3 of them had been treated with hemodialysis. We had no critical cases and patients have welcomed this solution. In addition, the costs related to the Assisted PD are lower in comparison with the costs of the hospital hemodialysis. Considering the reliability of the first results, ASL has decided to raise the economic contribution for this activity, allowing us to increase the number of patients to include in Assisted PD.


Awareness about tuberculosis in a rural area of Mandya district: A cross-sectional study in southern Karnataka.
Tuberculosis (TB) is a re-emerging disease in India. Creating awareness among the community still plays a vital role in preventing and controlling the spread of TB. A cross-sectional study was carried out for a period of 4 months in a rural area in Mandya, southern Karnataka. Sample size was estimated and those who fulfill the inclusion criteria were included with prior consent. Data were collected through interview method using structured questionnaire and analyzed using Epi info software. Among the 774 participants, majority (61.8%) of the study participants belonged to the age group of 30-59 years; 32.7% of the subjects had studied up to secondary level of education. More than three-fourth of the subjects (76.1%) had heard about TB disease. More than 50% of the subjects mentioned "coughing" by a diseased person as the main reason for spread. Forty percent of the subjects, opined as recovery, will be complete after treatment. More than 60% of the subjects knew that TB diagnosis and treatment is free in any government health center. Our study found that knowledge regarding TB and its control in many of the aspects is either insufficient or not satisfactory in the community.


Insights in Nanoparticle-Bacterium Interactions: New Frontiers to Bypass Bacterial Resistance to Antibiotics.
Nanotechnology has been revealed as a fundamental approach for antibiotics delivery. In this paper, recent findings demonstrating the superiority of nanocarried-antibiotics over "naked" ones and the ways by which nanoparticles can help to overwhelm bacterial drug resistance are reviewed. The second part of this paper sheds light on nanoparticle-bacterium interaction patterns. Finally, key factors affecting the effectiveness of nanoparticles interactions with bacteria are discussed.


Investigating the Electronic Portal Imaging Device for Small Radiation Field Measurements.
With the advent of state-of-the-art treatment technologies, the use of small fields has increased, and dosimetry in small fields is highly challenging. In this study, the potential use of Varian electronic portal imaging device (EPID) for small field measurements was explored for 6 and 15 MV photon beams. The output factors and profiles were measured for a range of jaw-collimated square field sizes starting from 0.8 cm × 0.8 cm to 10 cm × 10 cm using EPID. For evaluation purpose, reference data were acquired using Exradin A16 microionization chamber (0.007 cc) for output factors and stereotactic field diode for profile measurements in a radiation field analyzer. The output factors of EPID were in agreement with the reference data for field sizes down to 2 cm × 2 cm and for 2 cm × 2 cm; the difference in output factors was +2.06% for 6 MV and +1.56% for 15 MV. For the lowest field size studied (0.8 cm × 0.8 cm), the differences were maximum; +16% for 6 MV and +23% for 15 MV photon beam. EPID profiles of both energies were closely matching with reference profiles for field sizes down to 2 cm × 2 cm; however, penumbra and measured field size of EPID profiles were slightly lower compared to its counterpart. EPID is a viable option for profile and output factor measurements for field sizes down to 2 cm × 2 cm in the absence of appropriate small field dosimeters.


Biosynthesis of cholestanol in higher plants.
To understand the early steps of C(27) brassinosteroid biosynthesis, metabolic experiments were performed with Arabidopsis thaliana and Nicotiana tabacum seedlings, and with cultured Catharanthus roseus cells. [26, 28-2H(6)]Campestanol, [26-2H(3)]cholesterol, and [26-2H(3)]cholestanol were administered to each plant, and the resulting metabolites were analyzed by gas chromatography-mass spectrometry. In all the species examined, [2H(3)]cholestanol was identified as a metabolite of [2H(6)]campestanol, and [2H(3)]cholest-4-en-3-one and [2H(3)]cholestanol were identified as metabolites of [2H(3)]cholesterol. This study revealed that cholestanol (C(27) sterol) was biosynthesized from both cholesterol (C(27) sterol) and campestanol (C(28) sterol). It was also demonstrated that cholestanol was converted to 6-oxocholestanol, and campestanol was converted to 6-oxocampestanol.


Comparison of the Oral Steroids, Macrolides and Combination Therapy in Nasal Polyposis Patients.
In this study, our aim was to compare oral steroid therapy with macrolide therapy and with oral steroid + macrolide (combine) therapy in patients with nasal polyposis (NP). All patients were treated with nasal steroid therapy for eight weeks and divided randomly into three groups as follows: Oral steroid group, oral macrolide group and combine group. All patients underwent endoscopic staging, radiological grading, odour testing and completed the sino-nasal outcome test-22 (SNOT-22) questionnaire before and after treatment. Significant improvement was observed in all parameters after treatment in all three groups. All parameters were significantly better in the combined group than in the macrolide group. Comparison of the oral steroid group and macrolide group revealed significantly better radiological grading and odour test changes for the oral steroid group, but no statistically significant differences existed according to endoscopic staging and SNOT-22. The post-treatment SNOT-22 score was significantly better in the combined group than in the steroid group. A comparison of the combined and steroid groups showed better results for the combined group for all parameters, but the differences were not significant. All treatment protocols were effective and the successful use of macrolide indicates its potential as an alternative in patients with contraindications to oral steroid treatment. The combined treatment may demonstrate significantly better results than steroid treatment alone if larger studies with more patients are performed.


[Medicines: if their added value is not made explicit.]
Information on added therapeutic value of medicines should represent the basis for therapeutic decisions and ideally, before of that, for drug registration. A recent study assessed the availability and quality of such information provided by Medicines Regulatory Authorities and other national public health institutions in 8 European countries, and of tools facilitating the implementation of such information. This study highlighted for UK and Germany quite an advanced framework of evidence-based, comparative drug information for health professionals, decision-makers and for the general public. Other countries (including Italy) seem far behind. More efforts are warranted to make this information available and to develop sharp formats to make it easier to understand and put in context. Coordinated efforts at European level can help in the efficient production of evidence-based material. Specific plans would then be necessary to favor its local implementation.


A revised map location for the histidine utilization genes in Pseudomonas putida.
The histidine utilization genes hutH and hutU of Pseudomonas putida ATCC 12633 have been mapped by interrupted mating and transduction to a location at approximately 43 minutes on the chromosome, closely linked to ser-800 and met-400 markers previously shown to be at 46 and 42 minutes, respectively. Since restriction enzyme mapping and cloning results have established that all genes associated with the hut pathway are contiguous, earlier maps of this strain which place these genes near 10 minutes on the chromosome in a superoperonic catabolic cluster are in error.


Optical vector analysis based on double-sideband modulation and stimulated Brillouin scattering.
A high-resolution and high-accuracy optical vector analysis based on optical double-sideband modulation and stimulated Brillouin scattering is proposed and experimentally demonstrated. Different from the conventional OVA based on optical single-sideband modulation, in which the measurement range is limited by the bandwidth of the microwave and optoelectronic components, and the measurement accuracy is restricted by the high-order sidebands, the proposed technique measures the magnitude and phase responses by making use of both ±1st-order sidebands without spectrum response aliasing. As a result, the measurement range is doubled, and the high-order, sideband-induced errors only appear at specific frequencies that are predictable and removable. A proof-of-concept experiment is carried out. The transmission response of a fiber Bragg grating, in a range of 80 GHz, is measured with a resolution of less than 667 kHz by using 40 GHz microwave components.


Dichotomy between the induction of suppressor cells and immunologic tolerance by adult thymectomy.
Adult thymectomy prevents the development of suppressor T cells without impairing the induction of immunologic tolerance to the same antigenic determinant. This finding demonstrates that the cellular mechanisms underlying immune suppression and immune tolerance are different.


Single-Cell RNA Sequencing Reveals the Cellular Origin and Evolution of Breast Cancer in BRCA1 Mutation Carriers.
The cell of origin and the development of breast cancer are not fully elucidated in BRCA1 mutation carriers, especially for estrogen receptor (ER)-positive breast cancers. Here, we performed single-cell RNA sequencing (RNA-seq) on 82,122 cells isolated from the breast cancer tissues and adjacent or prophylactic normal breast tissues from four BRCA1 mutation carriers and three noncarriers. Whole-exome sequencing was performed on breast tumors from the four BRCA1 mutation carriers; for validation, bulk RNA-seq was performed on adjacent normal breast tissues from eight additional BRCA1 mutation carriers and 14 noncarriers. Correlation analyses suggested that breast cancers in BRCA1 mutation carriers might originate from luminal cells. The aberrant luminal progenitor cells with impaired differentiation were significantly increased in normal breast tissues in BRCA1 mutation carriers compared with noncarriers. These observations were further validated by the bulk RNA-seq data from additional BRCA1 mutation carriers. These data suggest that the cell of origin of basal-like breast tumors (ERneg) in BRCA1 mutation carriers might be luminal progenitor cells. The expression of TP53 and BRCA1 was decreased in luminal progenitor cells from normal breast tissue in BRCA1 mutation carriers, which might trigger the basal/mesenchymal transition of luminal progenitors and might result in basal-like tumor development. Furthermore, ERhigh luminal tumors might originate from mature luminal cells. Our study provides in-depth evidence regarding the cells of origin of different breast cancer subtypes in BRCA1 mutation carriers. SIGNIFICANCE: Single-cell RNA-seq data indicate that basal-like breast cancer (ERneg) might originate from luminal progenitors, and ERhigh luminal breast cancer might originate from mature luminal cells in BRCA1 mutation carriers.


Distribution of pre-mRNA splicing factors at sites of RNA polymerase II transcription.
If pre-mRNA splicing begins during RNA synthesis, then transcriptionally active genes may be expected to contain high concentrations of pre-mRNA splicing factors. However, previous studies have localized splicing factors to a network of "speckles," which is distinct from individual sites of gene transcription where pre-mRNA is spliced. Speckles have been detected with antibodies specific for splicing snRNPs and members of the SR family of splicing factors. Here we report that dilution of these probes results in the visualization of hundreds of sites throughout the HeLa cell nucleus, the size and distribution of which are consistent with transcription units viewed with light microscopy. Importantly, these sites of highest SR protein concentration frequently coincide in three-dimensional space with active sites of RNA polymerase II transcription. A newly developed reagent specific for a single member of the SR family, SRp20, detects a subset (approximately 20%) of these sites, suggesting the gene-specific accumulation of these splicing regulators, which have distinct functions in pre-mRNA splicing. These observations question the view that the nucleus and its functions are highly compartmentalized; instead, they support a model in which the localization of these and possibly other gene regulators is determined primarily by their function.


Treatment of mediastinitis using an open irrigation and delayed sternal reconstruction with a pectoralis major muscle flap.
Mediastinitis is a very serious complication after cardiac surgery. To date, the optimal treatment of mediastinitis is still controversial: the "closed wound" procedures and the "open wound" treatments are the two conventional modalities reported in the literature. Between January 1995 and December 2000, 20 patients, who had previously been submitted to cardiac surgery, were treated by a modification of the "open wound" treatment strategy for postoperative mediastinitis. All patients were scheduled for 2, 6, and 12-month clinical follow-up. The procedure performed consisted of three major steps: 1) early sternum reopening, followed by phase 2) including irrigation of the wound 3 times daily, and the final step 3) of delayed reconstructive surgery using the pectoralis major myocutaneous advancement flap closure technique. We prospectively analyzed the short- and long-term results of these procedures. The overall duration of hospitalization was 25 +/- 10 days; no patient required intensive care unit permanency. Clinical success was achieved in all 20 cases (100%). No recurrences of local (such as fistulas or abscesses) or systemic infections were noted, and no patient required sternal reopening during follow-up. An optimal cosmetic result was obtained in all patients and only 2 cases had persistent sternal pain regressing at the 6-month follow-up control. Our data suggest that for patients with severe mediastinitis, this treatment strategy is safe. The clinical and esthetic success rates are high, the recovery time rapid, and the rates of short- and long-term complications very low.